Trabectedin (T) versus adriamycin plus dacarbazine (A-DA) in advanced solitary fibrous tumor (SFT): Results from a phase II randomised clinical study (STRADA).
Authors: Silvia Stacchiotti, Giovanni Grignani, Bruno Vincenzi, Ignazio Carreca, Emanuela Palmerini, Paola Collini, Angelo Paolo Dei Tos, Gianpaolo Dagrada, Nadia Zaffaroni, Alessandro Gronchi, Gianluca Ignazzi, Viviana Appolloni, Matilde Ingrosso, Anna Maria Frezza, Paolo Giovanni Casali, Carlo Morosi, Luigi Mariani, Giacomo Giulio Baldi
Journal: Journal of Clinical Oncology (2023)

11571 Background: T and A-DA showed antitumor activity in a PDX model of dedifferentiated-SFT (D-SFT) and a few cases of activity in advanced SFT pts have been reported. The efficacy of these agents in advanced typical- (T-)/ malignant- (M-)SFT is unclear. A phase 2 randomised (R) study was conducted within the Italian Sarcoma Group (ISG) to investigate the activity of T and A-DA in advanced T-, M- and D-SFT (Clin-Gov: NCT03023124). Methods: An Italian, multicentre, investigator-initiated prospective open-label, R, non-comparative, phase 2 trial was started in July 2017 involving 6 ISG sites, to evaluate the activity of front-line T (1,5-1,3 mg/sqm at investigator’s discretion, day 1 every 3 wks; arm A) vs A-DA (A 75 mg/sqm day 1 + DA 400 mg/sqm days 1,2 every 3 wks; arm B) in &gt; 18 years-old pts with advanced SFT (T-SFT, M-SFT, D-SFT) until progression or limiting toxicity; in arm B, a maximum number of 6 cycles was foreseen, given the constrain of the maximum tolerated dose of A. Eligible pts had to show RECIST progression in the 6 mos prior to study entry. Centralized pathologic and radiologic review was performed. Pts were randomly assigned to Arm A or Arm B (1:1 ratio), with cross over in case of progression (PD) or unacceptable toxicity prior to the completion of the 6 cycles (arm B in case of randomization to arm A and vice versa). An interim analysis was pre-planned after reaching 10 evaluable pts in each arm, and at least 1 response in arm A was required to continue the study. Primary end-point was the overall response rate (ORR) by RECIST; secondary end-points ORR by Choi, progression-free survival (PFS), overall survival (OS). Results: Enrolment for the interim analysis was completed in September 2022. 30 pts were screened and 23 were enrolled (7 screening failure): T-SFT = 7, M-SFT = 14, D-SFT = 2. All pts were naïve; 3 pts are ongoing, 20 completed their treatment (12 = PD, 8 = other). All pts were evaluable for RECIST. No responses by RECIST were seen in each arm (ORR 0%), while stable disease (SD) and PD were 9 (45%) and 1 (5%) in arm A and 8 (40%) and 2 (10%) in arm B, respectively. At a 15.9-mo (I.Q. range 11.3-29.0) m-FU, m-PFS by RECIST was 9.2 (2.7-not assessable) mos in arm A and 8.0 (1.1-not assessable) mos in Arm B, with 29.6% progression-free pts at 1 year in arm A and 18.7% in arm B. Median OS was 34.3 (9.3-not assessable) mos in arm A, 31.5 (4.2-31.5) mos in arm B. Conclusions: No responses were seen neither to T nor to A-DA across all SFT subtypes; therefore, the study was closed to enrolment for T-SFT and M-SFT after the interim analysis. Noteworthy, both T and A-DA stabilised the disease in about 40% of previously progressive pts, and nearly 30% of pts treated with T were free from progression at 1 year. On the other hand, no conclusion can be drawn yet on the activity of T / A-DA in this SFT subtype, since D-SFT cases who entered the study were only 2 and the enrolment of D-SFT is still ongoing. Clinical trial information: NCT03023124 .